The applicant plans to continue studies aimed at understanding at a molecular level the pathogenesis of reovirus infections in mice. This will entail looking at the nature of reovirus interactions with the heart to develop a workable model of viral induced myocarditis. We will examine the liver and biliary tract to see if reovirus is excreted into the bile. Mutants in the hemagglutinin of reovirus 1 will be generated to study the pathogenesis of T1 infection. We will attempt to identify the genetic basis for difference in lethality of reovirus 3 by peripheral inoculation as compared to direct CNS inoculation. We will study interferon to determine if differences in induction of interferon in vitro explain certain differences in viral virulence following P.O. inoculation. Studies will be performed on cell cultures to determine the mechanism of neutralization of reovirus 1 and 3. In addition we will analyze the movement of reovirus into endosomes to understand what regulates early events in reovirus infection. We will study reoviruses in normal and transformed cells to determine how oncogenes alter the growth cycle of reoviruses. Lastly we will continue to sequence genes playing a role in viral virulence as well as biological variants in these genes. These studies should help explain some of the in vivo phenomenon in molecular detail.